Calcium is an important mediator of the secretory process in a variety of cell types, however, the mechanism(s) by which Ca 2 ion exerts its primary action is unclear. I will try to define the role of Ca 2 ion in insulin secretion by exploring its interaction with other putative mediators of secretion, namely the prostaglandins (PGs) and cyclic nucleotides (cGMP and cAMP). I propose to extend my previous research on the adrenal cortex to the pancreatic beta-cell where Ca 2 ion may also be involved in phospholipase activity, and PG and cyclic nucleotide biosynthesis. The degree of dependence of insulin synthesis and release on PG and cyclic nucleotide metabolism will also be determined. These studies will be carried out on isolated rat pancreatic islets and will involve a variety of radioimmunoassays, including PGs, cyclic nucleotides, and insulin. Phospholipase A2 activity will also be studied in this tissue. The effects of glucose and other insulin secretagogues on phospholipase A activity, and PG and cyclic nucleotide metabolism will be investigated in the presence and absence of Ca 2 ion. Moreover, I will study changes in insulin release from islets exposed to PG synthesis inhibitors and agents which specifically increase cGMP levels. It is anticipated that the functional relationships developed as a result of this investigation will help to define the role of Ca 2 ion in insulin secretion, and provide deeper insight into the fundamental mechanisms which control secretory processes.